Introduction: Although patients with an acute increase in airflow resistance may require aerosol therapy and noninvasive positive pressure ventilation (NIPPV), the efficiency of different aerosol devices and masks during NIPPV is not well understood. The purpose of this study was to determine the efficiency of a jet nebulizer (JN), a vibrating mesh nebulizer (VMN) and a pressurized metered-dose inhaler (pMDI) and three different masks during NIPPV. Method: An in vitro lung model consisted of the upper airway of an adult teaching manikin with a collecting filter at the level of the bronchi attached to a passive test lung. NIPPV was administered via full face mask for the first experiment (AF531 oro-nasal) with an IPAP/EPAP of 20/5 cm H2O and a respiratory rate of 15 Breath per minute (BPM). Aerosol generators were placed between the leak in the circuit and the mask. Albuterol sulfate (2.5 mg/ 3 ml) was nebulized with the JN (Micromist) and the VMN (Aeroneb Solo). Four puffs (108 µg/puff) were administered with the pMDI (ProAir HFA) with a spacer (Aerovent) that first was placed in the recommended normal position (pMDI-N) with aerosol plume directed towards patient, and then in the reversed position (pMDI-R), with aerosol directed away from patient (n=3). In the second experiment, three masks were used 1) the Performax mask, 2) the AF531 oro-nasal mask, and 3) the Performa track mask. Performa track mask was tested with only Aeroneb solo while other masks were tested with both Aeroneb solo and NIVO VMNs. In both experiments, filters were eluted with 0.1 HCl and analyzed by a spectrophotometer at 276 nm. Residual volumes were determined gravimetrically. Result: Descriptive statistics, one-way analysis of variance (ANOVA), and independent t tests were used. Statistical significance was set at p<0.05. During NIPPV, inhaled mass (IM) and inhaled mass percent (IM %) varied significantly (p=0.042 and p=0.028, respectively). Aerosol delivery with the JN was the lowest during NIPPV. The VMN has a significantly lower residual volume than the JN (p=0.0001). No statistical difference in efficiency was found between the two pMDI orientations (p=0.253). In the second experiment, oro nasal mask with Aeroneb Solo VMN results in the highest IM which was significant when compared with all other masks(p=0.0001). No statistical difference can be found between other masks. Conclusion: The JN was less efficient than the VMN and the pMDI in either orientation. The type of aerosol device used during NIPPV influenced aerosol delivery in this simulated adult lung model. Oro nasal mask with Aeroneb Solo VMN provided the highest IM.